How Starbucks, statins, and sleep may affect the brain, and more
Happy New Year! It’s time to whip out ye olde list of resolutions. But, remember that working on your mind is just as important as working on your body, and might even be easier. Here’s a list of foods to protect from cognitive decline.
So, what’s happened in the world of neurology while you were off sipping hot chocolate beside the fireplace this past week? Well, for one thing, researchers at Northwestern University are looking into the science of what exactly makes Starbucks and other rewards programs so enticing. Surely it’s more than just good coffee on the brain. And speaking of coffee, you might wanna grab another cuppa’ joe. Turns out that too much sleep may have some life-threatening effects.
But it’s not all bad news, researchers have also finally identified the region of the brain where Alzheimer disease first starts, the neuroprotective capabilities of statins, two drugs to stop age-induced brain damage, and more.
Read this week’s Neuro Brief to get the full updates.
The Edwin Smith Surgical Papyrus contains the earliest reference to the brain, albeit in hieroglyphs. Written in ancient Egypt in the 17th century BC by a battlefield surgeon who assessed the symptoms, diagnosis, and prognosis of two patients who sustained head trauma, this document demonstrated that ancient Egyptians had some knowledge of the effects of head trauma. The author described aphasia and seizures following injuries, as well as “pulsations of the exposed brain” and compared the brain’s surface to that of copper slags. The hieroglyph for brain was found eight times in this ancient papyrus script.
In the News
Unearthing the origins of AD. Where does Alzheimer disease (AD) start? Researchers at the Universities of St. Andrews and Edinburgh may have just found out. They pinpointed the lateral entorhinal cortex (LEC) as one of the first brain areas to show changes from AD.
Specifically, they found that when the connection between one of the LEC’s layers—of which there are many—and the hippocampus is not functioning properly, episodic memory is affected, but not simpler forms of memory. Episodic memory is one of the first things to go in AD patients.
This is fantastic news because researchers now have a target to shoot for in developing new treatments for the damage caused by AD.
Put down that drink. In patients with AD with a mutation in aldehyde dehydrogenase 2 (ALDH2)—an enzyme involved in alcohol metabolism—having a stiff drink could increase cellular damage.
The ALDH2 mutation is associated with facial flushing—a rosy red glow frequently called the “Asian glow”—after drinking alcohol. ALDH2 is a great cleaner-upper of acetaldehyde—a toxic product of alcohol metabolism—but in those with this mutation, its “cleaning” ability is greatly reduced. Thus, in people with this mutation, drinking causes an acetaldehyde build up, and the body responds with skin flushing and inflammation. The “Asian glow” occurs in about 8% of the world’s population.
Researchers studied cell cultures from the cells of 20 AD patients. Those with the ALDH2 mutation could not break down acetaldehyde as well as those without the mutation. To add insult to injury, these ALDH2 mutant cells contained more free radicals and more 4-HNE—another toxic chemical usually processed by “normal” ALDH2. Too bad, because this could lead to aldehyde accumulation and cellular damage to the mitochondria, as well as neuronal apoptosis.
But, researchers were happy to find that adding Alda-1—a small molecule that repairs the ALDH2 mutation—lowered free radical levels even after adding alcohol, leading them to surmise that alcohol can damage the cells normally protected by ALDH2, and—not good—this damage is greater in cells from patients with the ALDH2-mutated form of AD.
So, the interplay between alcohol and these AD-related genes is an important one. In those with this mutation, drinking alcohol may not only increase the risk of AD, but may induce faster progression in those already affected by the disease.
Why Starbucks Rewards work. Researchers at Northwestern University’s Lerner Laboratory are using mice to study how and why habits are formed on both the behavioral and neural levels. Habits as benign-but-compulsive as your daily Starbucks fix, and those as damaging as an addiction to heroin. Part of the research also seeks to understand why rewards programs—like those used at Starbucks or Walgreens—are so successful and keep customers coming back for more. Besides addiction, researchers are also interested in other mental health disorders that involve compulsive behaviors. We’ll let you know when the results are in. Until then, don’t question why you need that Iced White Chocolate Mocha, just enjoy it!
A dementia calculator? What if you could use a simple tool to see the severity of a patient’s dementia at the point of diagnosis, or even calculate their life expectancy? Swedish researchers may have just found such a tool. In their study of over 50,000 individuals from the Swedish Dementia Registry between 2007 and 2015, they assessed the effect of several easy-to-identify characteristics on life-expectancy following diagnosis. Their results helped them come up with two schematic tables.
The first table is for PCPs and gives a prognosis upon a diagnosis of dementia based on sex, age, cognitive ability (using the MMSE), and comorbidity (via the Charlson Comorbidity Index). The second table is for neurologists and other specialists, and factors in the patient’s dementia subtype. Using these tables, clinicians can get a clearer picture of which patients will likely expire within 3 years of their dementia diagnosis.
Ultimately, researchers hope the tool can be used to differentiate between patients to better understand who needs a care plan and who would benefit from additional monitoring.
Dealing with Duchenne. In more good news, the FDA has granted accelerated approval to injectable golodirsen (Vyondys 53) for the treatment of patients with Duchenne muscular dystrophy (DMD) with a confirmed mutation of the dystrophin gene amenable to exon 53 skipping—seen in roughly 8% of DMD patients.
Although a rare genetic disorder, DMD is the most common of the muscular dystrophies, and is caused by a lack of dystrophin, the protein that keeps muscle cells intact. Until now, there have been no treatments targeted specifically to this subtype of the disease.
Golodirsen—manufactured by Sarepta Therapeutics—was also given an orphan drug designation, which offers incentives to develop drugs for rare diseases. Sarepta also received a rare pediatric diseases priority review voucher from the FDA, which also encourages the development of new drugs/biologics for rare diseases in children.
Statins strike again! Here’s another example of why statins may just be the wunderkind of all drugs. They may have—researchers have found—neuroprotective benefits for patients who suffer spontaneous intracerebral hemorrhage (ICH). Their results are published in Neurology.
What’s behind the protective power of statins in this setting? It’s likely their ability to target secondary brain injury pathways in the surrounding parenchyma of the brain. By downregulating mevalonate and its derivatives, statins target cell signaling pathways in control of proliferation, adhesions, cytokine production, and reactive oxygen species generation. Preclinical and retrospective clinical studies are supportive of this effect, as are findings some clinical studies, in which researchers have shown lower mortality and improved functional outcomes with statin use after ICH.
More studies are needed, but feel free to view statins in a whole new light from now on.
Can we stop age-induced brain damage? While studying two investigational drug candidates—CMS121 and J147—to see whether they improved memory and slowed cell degeneration in preclinical models of Alzheimer disease (AD), researchers found that they may also be handy in healthy controls as well. CMS121 and J147 seem to block the damage to brain cells caused by simple aging.
CMS121 and J147 are variants of plant compounds that have medicinal properties, and have been shown to keep neurons alive even after they are exposed to cellular stressors such as aging and AD. And mice treated with these two agents not only did better on memory tests than controls, but showed cellular and molecular differences—including mitochondrial preservation despite aging.
Studies in humans have shown that mitochondrial function is impacted by aging, and gets even worse with AD. These results show that CMS121 and J147 protect mitochondria by upping levels of acetyl-coenzyme A, thereby protecting the brain cells against the normal molecular ravages of aging. Stay young, people!
New in Patient Management
Careful how you sleep. Patients with a higher REM seizure burden may have worse epilepsy outcomes, according to a new study.
Non-REM sleep may promote seizures and interictal epileptiform discharges (IED). It seems that when patients are admitted to an epilepsy monitoring unit (EMU), their REM spike burden (RSB)—the proportion of REM occupied by IED or seizures—can be assessed and become an important new biomarker to determine which patients will have greater peak seizure frequency overall.
Researchers studied 63 patients admitted to an EMU, who spent a mean of 6.4 days there. They found no association between duration of REM and any outcomes, but did find a significant association between RSB and peak seizure frequency. For each 1% increase in RSB, patients had 1.69 additional seizures per month (P = 0.007).
Breakthrough REM IED and seizures in the EMU may one day be an important complementary biomarker that shows the burden and/or severity of epilepsy.
You snooze, you lose. Too much sleep may be as bad as too little sleep. According to a recent study in Neurology, taking long daytime naps or sleeping for 9 hours or more at night may increase your risk of stroke. In fact, stroke was 25% more likely to occur in people who took regular midday naps that lasted more than 90 minutes compared with those who snoozed for only 1 to 30 minutes. And those who got 9 or more hours of ZZZZ’s per night were 23% more likely to have a stroke than those sleeping 7 to less than 8 hours per night.
The news gets worse for those who were both long nappers and long sleepers—they were 85% more likely to have a stroke than more moderate nappers and sleepers. And in those who reported poor sleep quality, the risk of stroke was 29% more likely than those with good sleep.
Drummers do it better? Playing the drums may have incredible effects on the structure of the brain. Drummers who have played regularly for years have fewer but thicker fibers in the corpus callosum, and have more organized and efficient motor brain areas, according to a recent study.
Playing musical instruments has long been known to change the brain through neuroplastic processes, but no one had ever specifically studied what playing the drums did. Because drummers have far superior motor coordination, such as playing different rhythms with each hand simultaneously, these researchers were interested in finding out why drummers can do things that are impossible for the rest of us.
They compared MRIs from 20 professional drummers (with a mean of 17 years of drumming experience, and over 10 hours of practice per week) with those from 24 non-musical controls.
They found that the drummers’ thicker fibers in the corpus callosum allowed for enhanced info exchange between the left and right hemispheres. And the thicker the better: thicker fibers = better drumming! Something John Bonham, Keith Moon, and Ginger Baker will never know. But then again, they didn’t need to know—they were just the best.
Plus, researchers also found that drummers were guilty of sparse sampling—ie, better and more efficient brain organization in motor task areas, leading to less-but-more efficient neurological activity than controls could achieve.
You’ll be happy to know that researchers are now conducting a follow-up study on what long-term drumming does to the brain, and they’re looking for drummers and non-musicians aged 45-70 years. Whether you’re a drummer or not, this may just be a fun study to volunteer for.
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46th Annual Meeting of the Southern Clinical Neurological Society (SCNS) CME, in Naples, FL, January 18-22, 2020
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